Huntington’s Disease: Neuropathological Grading

  • Jean-Paul Vonsattel
  • Richard H. Myers
  • Thomas J. Stevens
  • Robert J Ferrante
  • Peter A. Paskevich
  • Edward P. RichardsonJr.
  • Edward D. Bird
Part of the Advances in Behavioral Biology book series (ABBI, volume 32)


The striatum was found to exhibit marked variation in the severity of neuropathological involvement in post mortem brain specimens from 163 clinically diagnosed cases of Huntington’s disease (HD). A grading system was established by macroscopic and microscopic criteria, resulting in five grades (0–4) designated in ascending order of severity. The earliest changes were seen in the medial caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. The grade correlated with the extent of clinical disability as assessed by a rating scale. Quantitative measurements revealed a 50% neuronal loss in the CN in grade 1 and a 95% loss in grade 4. Astrocytes are greatly increased in grades 2–4. Analyses of the CN in grade 4 reflect mainly astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1–2, these regions would reflect early cellular and biochemical changes in HD.


Nucleus Accumbens Neuronal Loss Caudate Nucleus Globus Pallidus Brodmann Area 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alzheimer A., 1911, Ueber die anatomische Grundlage der Huntingtonschen Chorea und der choreatischen Bewegungen ueberhaupt, Neurol Centralblatt 761, 30:891–892.Google Scholar
  2. Anton G., 1896, Ueber die Beteiligung der grossen basalen Gehirnganglien bei Bewegungsstoerungen und insbesondere bei Chorea, Jahrblatt Psychiat Neurol (Lpz), 14:141–181.Google Scholar
  3. Arendt T, Bigl V, Arendt A, Tennstedt A., 1983, Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s disease, Acta Neuropathol (Berl), 61:101–108.CrossRefGoogle Scholar
  4. Beal MF, Ellison DW, Mazurek MF et al., 1986, A detailed examination of substance P in pathologically graded cases of Huntington’s disease, Neuroscience — Abstr., 12:565.Google Scholar
  5. Beal MF, and Martin JB., 1986, Neuropeptides in neurological disease, Annals of Neurology, 20:547–565.PubMedCrossRefGoogle Scholar
  6. Bielschowsky, M., 1919, Einige Bemerkungen zur normalen und pathologischen Histologie des Schweif- und Linsenkerns, Journal Fuer Psychologie und Neurologie, 25:1–13.Google Scholar
  7. Birnbaum G., 1941, Chronisch-progressive Chorea mit Kleinhirnatrophie, Archiv fuer Psychiatrie und Nervenkrankheiten, 114:161–182.Google Scholar
  8. Bugiani O, Tabaton M, Cammarata S., 1984, Huntington’s disease: Survival of large striatal neurons in the rigid variant, Ann Neurol, 15:154–156.PubMedCrossRefGoogle Scholar
  9. Bruyn GW., 1986, Huntington’s chorea; historical clinical and laboratory synopsis, in: Vinken PJ, Bruyn GW ed., Handbook of Clinical Neurology 6:379–396.Google Scholar
  10. Bruyn GW, Bots G Th AM, Dom R., 1979, Current Neuropathological Status. In: Chase TN, Wexler NS, Barbeau A. ed., Huntington’s chorea, Adv Neurol, New York: Raven Press, 23:83–93.Google Scholar
  11. Byers RK, Gilles FH, Fung C., 1973, Huntington’s disease in children. Neuropathologic study of four cases, Neurology, 23:561–569.PubMedGoogle Scholar
  12. Campbell AMG, Corner B, Norman RM, Urich H., 1961, The rigid form of Huntington’s disease, J Neurol Neurosurge Psychiat, 24:71–77.CrossRefGoogle Scholar
  13. Carpenter MB, Sutin J., 1983, Human Neuroanatomy, 8th ed., Baltimore/London: Williams & Wilkins, pp 536–538.Google Scholar
  14. De La Monte SM, Vonsattel JP, Hedley-Whyte ET, Ulcickas M, Richardson EP, Jr., 1987, Global loss of cerebral cortex and white matter volume in Huntington’s disease (HD), J. Neuropath Exper Neurol, in press.Google Scholar
  15. Dom R, Baro F, Brucher JM., 1973, A cytometric study of the putamen in different types of Huntington’s chorea, in: Barbeau A, Chase TN, Paulson GW ed. Huntington’s chorea, Adv Neurol., Raven Press, New York, 369–385.Google Scholar
  16. Dom R, Malfroid M, Baro F., 1976, Neuropathology of Huntington’s chorea, Neurology, 26:64–68.PubMedGoogle Scholar
  17. Dunlap CB., 1927, Pathologic changes in Huntington’s chorea with special reference to the corpus striatum, Arch Neurol Psychiat (Chicago), 18:867–943.Google Scholar
  18. Earle KM., 1973, Pathology and experimental models of Huntington’s chorea, in: Barbeau A, Chase TN, Paulson GW ed. Huntington’s chorea, Adv Neurol. New York: Raven Press, 1:341–351.Google Scholar
  19. Fau R, Chateau R, Tommasi M, Groslambert R, Garrels S, Perret J., 1971, Etude anatomo-chimique d’une forme rigide myoclonique de maladie de Huntington infantile, Rev Neurol, 124:353–366.Google Scholar
  20. Ferrante RJ, Kowall NW, Beal MF et al., 1985, Selective sparing of a class of striatal neurons in Huntington’s disease, Science, 230:561–563.PubMedCrossRefGoogle Scholar
  21. Ferrante RJ, Kowall NW, Richardson EP, Jr. et al., 1986, Topography of enkephalin substance P and acetylcholinesterase staining in Huntington’s disease striatum, Neuroscience Letters, 71:283–288.PubMedCrossRefGoogle Scholar
  22. Ferrante RJ, Beal MF, Kowall NW et al., 1987 (A), Sparing of acetylcholinesterase containing striatul neurons in Huntington’s disease, Brain Research, In Press.Google Scholar
  23. Ferrante RJ, Kowall NW, Beal MF et al., 1987 (B), Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington’s disease, Journal of Neuropathology & Experimental Neurology, 46:12–27.CrossRefGoogle Scholar
  24. Forno LS, Jose C., 1973, A pathological study, in: Barbeau A, Chase TN, Paulson GW ed. Huntington’s chorea, Adv Neurol, New York: Raven Press, 1:453–470.Google Scholar
  25. Golgi C., 1874, Sulla alterazioni delgli organi centrali nervosi in uno caso di corea gesticulatoria assoziata ad alienazione mentale, Riv Clin di Bologna, 4:361.Google Scholar
  26. Graybiel AM., 1986, Neurotransmitters in the basal ganglia: chemoarchitecture of the striatum in health and disease, (Abstract), in: Proceedings of the Xth International Congress of Neuropathology, Stockholm: Gotab, 88.Google Scholar
  27. Gusella JF, Wexler NS, Conneally PM et al., 1983, A polymorphic DNA marker genetically linked to Huntington’s disease, Nature, 306:234–238.PubMedCrossRefGoogle Scholar
  28. Hayden MR., 1981, Huntington’s chorea, Springer-Verlag, Berlin-Heidelberg.CrossRefGoogle Scholar
  29. Hallervorden J., 1957, Huntingtonsche Chorea (Chorea chronica progressiva hereditaria), in: Scholz W ed., Handbuch der Speziellen Pathologischen Anatomie und Histologie, Springer-Verlag: Berlin, Gottingen, Heidelberg, 13:793–822.Google Scholar
  30. Jelgersraa G, 1908, Neue anatomische Befunde bei Paralysis agitans und bei chronischer Chorea, Neurol Centralblatt 761, 27:995–996.Google Scholar
  31. Jervis GA., 1963, Huntingtons chorea in childhood, Arch Neurol 9:244–256.PubMedCrossRefGoogle Scholar
  32. Jeste DV, Barban L, Parisi J., 1984, Reduced Purkinje cell density in Huntington’s disease, Exp Neurol, 85:78–86.PubMedCrossRefGoogle Scholar
  33. Kalkhof J, Ranke O., 1913, Eine neue Chorea Huntington-Familie, Z. Ges Neurol Psychiat, 17:256–302.CrossRefGoogle Scholar
  34. Kiesselbach G., 1914, Anatomischer Befund eines Falles von Huntingtonscher Chorea, Monatsschr Psychiat und Neurol, 35:525–543.CrossRefGoogle Scholar
  35. Klintworth GK., 1973, Morphologic contributions of a century, in: Barbeau A, Chase TN, Paulson GW ed., Huntington’s chorea, Adv Neurol, Raven Press, New York, 1:353–368.Google Scholar
  36. Lange HW., 1981, Quantitative changes of telencephalon, diencephalon, and mesencephalon in Huntington’s chorea, postence-phalitic, and idiopathic parkinsonism, Verh Anat Ges, 75:923–925.Google Scholar
  37. Lange H, Thorner G, Hopf A, Schroder KF., 1976, Morphometric studies of the neuropathological changes in choreatic diseases, J Neurol Sci, 28:401– 425.PubMedCrossRefGoogle Scholar
  38. Lannois M, Paviot J., 1897, Deux cas de choree hereditaire avec autopsies, Arch Neurol, (Paris), 4:333–334.Google Scholar
  39. McCaughey WTE., 1961, The pathologie spectrum of Huntington’s chorea, J Nerv Ment Dis, 133:91–103.CrossRefGoogle Scholar
  40. Meynert Th., 1877, Discussion to Fritch, Psychiat Clb 7:47.Google Scholar
  41. Myers RH, Sax DS, Schoenfeld M, et al., 1985, Late onset of Huntington disease, J Neurol Neurosurg Psychiat, 48:530–534.PubMedCrossRefGoogle Scholar
  42. Pfeiffer JAF., 1913, A contribution to the pathology of chronic progressive chorea, Brain, 35:276–292.CrossRefGoogle Scholar
  43. Ramsay HJ., 1917, Progressive atrophy of the globus pallidus (primary atrophy of the pallidal system), Brain, 40:58–148.CrossRefGoogle Scholar
  44. Rodda RA., 1981, Cerebellar atrophy in Huntington’s disease, J Neurol Sci, 50:147–157.PubMedCrossRefGoogle Scholar
  45. Roizin L, Stellar S, Liu JC, 1979, Neuronal nuclear and cytoplasmic changes in Huntington’s chorea: Electron microscope investigations, in: Chase TN, Wexler NS, Barbeau A ed., Huntington’s chorea, Adv Neurol. Raven Press, New York, 23:95–122.Google Scholar
  46. Roos RAC, Pruyt JFM, de Vries J et al., 1985, Neuronal distributions in the putamen in Huntington’s disease, J Neurol Neurosurg & Psychiatry, 48:422–425.CrossRefGoogle Scholar
  47. Schroeder K., 1931, Zur Klinik und Pathologie der Huntingtonschen Krankheit, J Psychologie und Neurol, 43:183–201.Google Scholar
  48. Spielmeyer W., 1926, Die anatomische Krankheitsforschung am Beispiel einer Huntingtonschen Chorea mit Wilsonschem Symptomenbild, z Ges Neurol Psychiat 101:701–728.CrossRefGoogle Scholar
  49. Stone TT, Falstein EI., 1938, Pathology of Huntington’s chorea, J Nerv Men Dis, 88:602–626; 773–797.CrossRefGoogle Scholar
  50. Tagliavini F, Pilleri G., 1983, Basal nucleus of Meynert, J Neurol Sci, 62:243–260.PubMedCrossRefGoogle Scholar
  51. Terplan K., 1924, Zur pathologischen Anatome der chronischen progressiven Chorea, Virchows Arch Pathol Anat, 252:146–176.CrossRefGoogle Scholar
  52. Vonsattel JP, Myers RH, Stevens TJ, et al, 1985, Neuropathologic Classification of Huntington’s disease, J Neuropath Exp Neurol, 44:559– 577.PubMedCrossRefGoogle Scholar
  53. Walker FO, Young AB, Penney JB, Dovorini-Zis K, Shoulson I., 1983, Benzodiazepine and GABA receptors in early Huntington’s disease, Neurology, 34:1237–1240.Google Scholar
  54. Zalneraitis EL, Landis DMD, Richardson EP Jr, Selkoe DJ, 1981, A comparison of astrocytic structure in cerebral cortex and striatum in Huntington’s disease, Neurology 31:151.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Jean-Paul Vonsattel
    • 1
    • 2
    • 3
  • Richard H. Myers
    • 4
  • Thomas J. Stevens
    • 3
  • Robert J Ferrante
    • 1
    • 2
  • Peter A. Paskevich
    • 5
  • Edward P. RichardsonJr.
    • 1
    • 2
  • Edward D. Bird
    • 3
  1. 1.C.S. Kubik Laboratory for Neuropathology, James Homer Wright Pathology LaboratoriesMassachusetts General HospitalUSA
  2. 2.Department of Neurology-NeuropathologyHarvard Medical SchoolBostonUSA
  3. 3.Ralph Lowell Laboratories, Mailman Research CenterMcLean Hospital and Harvard Medical SchoolBelmontUSA
  4. 4.Department of NeurologyBoston University Medical School and Massachusetts General Hospital, Harvard Medical SchoolBostonUSA
  5. 5.Laboratories for Psychiatric Research, Mailman Research CenterMcLean Hospital and Harvard Medical SchoolBelmontUSA

Personalised recommendations